Smoke Inhalation in Veterinary Patients: Pathophysiology, Diagnosis, and Management
ABSTRACT
Smoke contains a mixture of harmful gases, chemicals, and superheated particles. Inhalation of smoke causes generalized hypoxia and airway inflammation due to impaired oxygen transport and utilization, as well as thermal and chemical injury in the airways. Generally, treatment is supportive with oxygen therapy and airway management, including chest physiotherapy, bronchodilators, and nebulization. Immediate oxygen therapy is mandatory for all suspected smoke inhalation patients and should not be delayed pending diagnostic test results or due to “normal” oxygen saturation readings that can be falsely elevated in carbon monoxide intoxication. Smoke inhalation patients with mild clinical signs who respond well to initial stabilization generally have a favorable prognosis. However, patients with severe signs or progression despite initial stabilization may require more advanced or intensive care.
Introduction
Based on the United States Fire Administration data, approximately 1.3 million fires resulted in 3800 human civilian deaths in 2021.1 Of these fire-related deaths, smoke inhalation injury was responsible for more than two-thirds of all fatalities.2–4 Smoke inhalation is associated with significantly longer hospital stays (11.4 vs 6.2 days) and increased mortality (8.54% vs 1.42%, respectively) in human burn patients, even with small burns.5 In contrast, fire victim animals are a less common presentation in veterinary emergency clinics, likely due to high mortality at the scene.6 Nevertheless, when these animals present, clinicians should be familiar with the pathophysiology and necessary interventions to rapidly and appropriately address smoke inhalation. This review provides information regarding the pathophysiology of smoke inhalation injury and summarizes the important points of stabilization and management in addition to presenting potential complications in veterinary patients.
Background
Smoke is a collection of small solid, liquid, and gas particles mixed in heated air produced by any type of fire.7,8 The composition of smoke mainly depends on the amount of available oxygen, the temperature generated, and the material burning. Combustion at a high temperature in an oxygen-rich environment completely incinerates materials and generates only a small amount of smoke that mainly consists of carbon (soot).7,9 In enclosed places, as in house fires, oxygen is consumed without rapid replenishment. This results in incomplete combustion of materials, producing toxic chemical intermediates.10,11
Carbon monoxide (CO) and hydrogen cyanide (HCN) are the most common toxic gaseous components of smoke.11 CO is produced by the incomplete combustion of organic materials, whereas HCN is a product of various nitrogen containing materials, including wool, silk, paper, rubber, and plastic.8,11 Smoke commonly contains other toxic chemicals, including ammonia, sulfur dioxide, phosgene, halogen acids, aldehydes, and halocarbons and several others.7,8,10 Fine particulate matter can also bind and carry chemicals deep into the airways, leading to direct tissue injury in the lungs.7 The most common chemicals in smoke and their effect on the body are listed in Table 1.
Pathophysiology
The major mechanisms of smoke inhalation injury are twofold. First, the systemic effects of inhaled toxic gases impede oxygen delivery and utilization. Second, the direct thermal and chemical insults cause massive inflammation of the respiratory system.2,9,12
Systemic effects (CO and HCN)
The simplified pathway of oxygen in health and in smoke inhalation are depicted in Figure 1. When smoke is inhaled, CO rapidly diffuses across the alveolar membrane and competes with oxygen for hemoglobin binding sites, forming carboxyhemoglobin (COHb).3,13,14 As CO’s affinity for hemoglobin is about 240 times higher than oxygen’s, it rapidly displaces oxygen on the hemoglobin, leading to decreased volumes of oxygen transported by hemoglobin (i.e., decreased oxygen carrying capacity), even if only a small amount of CO is inhaled.14,15 Additionally, CO reduces the ability of hemoglobin to release bound oxygen at the capillary level, further reducing the amount of oxygen delivered to tissues.15,16 Finally, CO binds to other heme-like molecules in the body, including myoglobin, platelet surface hemoproteins, and the cytochrome-c oxidase in the mitochondrial electron transport chain, thereby preventing normal function of these substances.3,13 As an example, inhibition of cytochrome-c oxidase results in decreased cellular energy production and increased free radical formation.13
Citation: Journal of the American Animal Hospital Association 60, 5; 10.5326/JAAHA-MS-7431
Another common toxic gas found in smoke is HCN, which is about 20 times more toxic than CO.9 Historically, HCN was used as a chemical weapon in World War I. Because it is lighter than air, HCN rapidly disperses in open spaces but in confined areas can quickly reach toxic levels.11 Cyanide is a strong inhibitor of mitochondrial cytochrome-c oxidase. By binding to its heme group, HCN renders cytochrome-c oxidase unable to use oxygen.17 Thus, HCN rapidly halts cellular energy production even in the presence of oxygen, causing severe organ dysfunction and eventually death if an animal is exposed to large doses.17,18
The combination of CO and HCN is synergistic, dramatically impairing aerobic metabolism of tissues.9 The resulting acute generalized systemic tissue hypoxia causes significant organ dysfunction, with brain and myocardial dysfunction primarily implicated as the immediate cause of death.3,11
Local effects (thermal and chemical injury)
Direct thermal injury caused by smoke inhalation mainly effects the upper airways.2,19 Ammonia, sulfur dioxide, and chlorine may dissolve in the moisture of the mucosa, forming caustic agents.7,9,11 The heat and chemical injury generate inflammation by the release of reactive oxygen species and various inflammatory mediators, including tumor necrosis factor α, interleukins (IL-1, IL-6, IL-8), histamine, serotonin, thromboxane, prostaglandins, and nitric oxide (NO).2,9 As a result, increased vascular permeability causes swelling and edema in the tissues, developing minutes to hours from exposure. The swelling can be severe enough to result in upper airway occlusion, usually within the first 24 hr.2,7
In the lower airways, smoke stimulates the sensory nerve endings. This leads to production of neuropeptides (e.g., Substance P, calcitonin gene–related peptide), which trigger reflex bronchoconstriction and inflammation.2,9,12 Inflammation will activate inducible nitric oxide synthetase, forming large amounts of NO. The resulting pulmonary vasodilation can increase pulmonary blood flow up to 10-fold above normal, markedly increasing pulmonary capillary hydrostatic pressure.2 Generation of NO will also lead to increased free radical formation, activation of the innate immune system, release of pro-inflammatory cytokines, and increased pulmonary capillary vascular permeabilty.2,9,19 These changes in capillary hydrostatic pressure and vascular permeability favor fluid leakage from the pulmonary vasculature into the interstitial and alveolar spaces, leading to pulmonary edema formation within the first 24 to 72 hr of exposure. 2,7,12 Additionally, the vasodilatory effect of NO prevents hypoxic pulmonary vasoconstriction, an important natural adaptation of the lung to alveolar hypoxia. This reflex normally allows the lungs to vasoconstrict and shunt blood away from poorly ventilated areas to better oxygenated regions, thus maintaining a favorable ventilation/perfusion ratio. Loss of this compensatory mechanism causes increased blood flow in hypoxic areas, leading to discrepancy between ventilation and perfusion (V/Q mismatch; V, ventilation; Q, perfusion) and worsening hypoxemia.2,19
Particulate matter (soot) carried in the smoke may also travel deep into the lower airways. Particles <1 to 3 μm diameter may even reach the alveoli.7 Armed with irritants on their surface, particulate matter can adhere to and damage pulmonary tissues. This damage increases airway secretions, inhibits mucociliary defense mechanisms, and leads to protein-rich exudate formation and leucocyte migration into the alveolar lumen.19 Moreover, the toxic chemicals also inactivate surfactant, causing the small alveoli to collapse.2,7,20 The resultant tissue swelling, pulmonary inflammation, and regional atelectasis exacerbates pulmonary edema.
Within 3 to 5 days of exposure, dying tracheal and bronchiolar epithelial lining mixed with inflammatory cells and fibrin can form pseudomembranous casts that slough into the airway lumen, causing mechanical obstruction.12 The resulting denudation of the airway mucosa compromises the normal barrier to infection. In addition, these casts become a nidus that enhances bacterial colonization of the upper and lower airways and contributes to secondary pulmonary infections.2,21
Ultimately, the combination of smoke’s detrimental effects on the respiratory system (upper and lower airway obstructions, pulmonary edema, atelectasis, loss of hypoxic pulmonary vasoconstriction, and secondary infections) can lead to acute hypoxemic and/or hypercapnic respiratory failure.2,6,9Figure 2 depicts a simplified diagram of the pathophysiology behind damage from smoke inhalation.
Citation: Journal of the American Animal Hospital Association 60, 5; 10.5326/JAAHA-MS-7431
Burn wounds
Animals with smoke inhalation injury may or may not have concurrent burn wounds from fire. Burns vary in their severity and need for medical care, but typically if >20% of the total body surface area is involved, severe systemic illness (e.g., burn shock) can result.22 Burn shock requires intensive medical and surgical management.22 Discussion of burn wounds and their management is beyond the focus of this article and can be found elsewhere.22,23 However, it is important to note that smoke inhalation injury coupled with burn wounds complicates the clinical picture, requiring more intensive care and leading to increased mortality.2,5,9,20 Smoke inhalation injury is considered an independent risk factor for mortality and is responsible for ≤20% increase in human burn victim mortality.21
History and physical examination findings
Smoke inhalation injury is diagnosed based on history with compatible clinical signs. A thorough history should be obtained as soon as possible, including information about the duration of exposure to smoke, type of smoke (e.g., open vs house vs industrial fire), animal’s neurological and respiratory status at the scene, time since smoke or fire exposure, treatment already provided by first responders, as well as routine patient data (including concurrent respiratory disease, heart disease, age, breed, etc). Clinical signs associated with the most common agents and localization are listed in Table 2.
Initial evaluation should focus on airway, breathing, circulation, and neurological assessment. Burns on the facial skin, singed whiskers/fur, and soot on the face and in the oral cavity raise concerns for severe smoke exposure.2,22 Thermal and chemical injury may not be evident immediately; therefore the clinician should monitor these patients for clinical signs of progressing upper airway obstruction, including erythema/edema in the oral mucous membranes and/or increased breathing effort accompanied by stertor/stridor.23
Systemic signs of hypoxia may manifest as tachypnea, tachycardia, hypotension, arrhythmias, and neurological dysfunction.6,22 The mucous membrane color can vary as a result of local and systemic vasodilation, however, most commonly appears normal. The “classic” cherry red mucous membranes associated with CO intoxication are rarely seen in living patients and are more commonly found as a post mortem finding in severe exposures.6,13,24 Therefore, the presence of “normal”—appearing (pink) mucous membranes should not be used as a surrogate to presume oxygen delivery is normal.
Initial mentation can range from extreme anxiety to depression, seizures, or coma. It is important to know that, even if mentation initially improves with therapy, CO intoxication can cause delayed neurological toxicity that can manifest days to weeks following exposure. Therefore, serial neurologic monitoring is recommended even after initial recovery.25–29
A thorough ophthalmic examination should be performed once the patient is systemically stable because exposure to heat and debris may cause inflammation of the conjunctiva and/or corneal injury.30 Gastrointestinal signs including ptyalism, nausea, vomiting, and diarrhea have also been reported in association with CO intoxication.23
Diagnostics and monitoring
Common point-of-care diagnostics for smoke inhalation patients often include packed cell volume/total solids, blood glucose, lactate, arterial or venous blood gas, electrocardiogram, and blood pressure measurement.
In the presence of CO, routine pulse oximeters will read a falsely elevated oxygen saturation despite a severe decrease in the blood oxygen content.3,13 The limitations of pulse oximetry in smoke inhalation patients are detailed in Box 1.16
A dedicated CO oximeter or specialized pulse oximeter is needed to measure COHb levels in the blood.3,6,31 Several point-of-care blood gas analyzers are built with a CO oximeter feature and can provide the COHb percentage in the blood. Reference intervals for COHb levels in healthy adult dogs are between 1.3% and 2.7%.31 In a case series of 21 dogs involved in a kennel fire, dogs showing respiratory signs at presentation had significantly higher COHb levels compared to those that were eupneic (31% vs 12%, respectively).29 To our knowledge, no reference ranges for COHb are available for healthy cats to date; a recent retrospective study reported COHb values of 2.15% (0.1%–4.4%) in hospitalized cats without respiratory disease.32
If CO oximetry is not available, clinical signs, including tachypnea, dyspnea, tachycardia, and/or altered mentation, in a smoke inhalation patient raises suspicion for elevated COHb levels, and immediate oxygen supplementation is warranted, even if oxygen saturation is “normal”.
Direct point-of-care measurement of blood cyanide is not available to date.17 Thus, the diagnosis of HCN poisoning is based on likelihood of exposure coupled with consistent clinical and laboratory abnormalities. In humans, HCN toxicity is considered likely in patients with a history of smoke inhalation if they have neurological signs with the presence of soot in the mouth, a plasma lactate level >8 mmol/L causing metabolic acidosis, and/or an arteriovenous oxygen saturation difference (difference between arterial oxygen content and central venous oxygen content) <10 mm Hg.17,21 If HCN toxicity is suspected, immediate treatment (see next section) is recommended because severe exposure can be fatal within minutes to hours.12,21
Acidosis is also common in smoke inhalation and is often a mixed respiratory and metabolic acidosis due to hypoventilation (high CO2 levels) and hyperlactatemia.6 Hypercapnia on a venous or arterial sample can be seen in patients with severe airway obstruction or with altered mentation leading to hypoventilation. Also, it is important to note that partial pressure of oxygen on an arterial blood gas (PaO2) sample may be normal despite the presence of CO and/or HCN because neither directly alters the dissolved oxygen content of the blood. Serial monitoring of arterial blood gas parameters, acid/base status, and blood lactate levels, along with frequent reassessment of respiratory and perfusion parameters, can guide further treatment.6,23,30
Imaging
Thoracic radiographs are useful to detect and monitor pulmonary injury. Thoracic imaging may be normal initially; repeating thoracic radiographs in patients with progressive clinical signs is recommended because radiographic changes often lag behind clinical signs.6 Diffuse, asymmetrical interstitial and alveolar patterns consistent with pulmonary edema are the most common finding, which may progress within the first 72 hr.2,23,30 Right middle lung lobe consolidation and pleural effusion have been reported in cats.30
Advanced imaging is not routinely used in veterinary patients with smoke inhalation, perhaps due to the need for anesthesia and related costs. However, thoracic computed tomography can be considered in patients with progressive respiratory signs.2,6,12 MRI of the central nervous system may be indicated in patients with neurological impairment that persists or worsens after initial stabilization.3,13 In humans, hyperintensities in the deep white matter may raise concern for long-term neurological impairment after CO poisoning.3,13
In humans, bronchoscopy is routinely used to confirm the diagnosis of smoke inhalation; it provides direct visualization and grading of the airway injury, which in turn is predictive of outcome.2,21 Moreover, bronchoscopy-guided broncho-alveolar lavage enables direct removal of casts and secretions and also allows sample collection for cytology and culture.2,21 Likely due to cost, availability, patient size limitations, and the need for general anesthesia, bronchoscopy has not been reported as a routine diagnostic used in veterinary patients with smoke inhalation injury.
Stabilization and management
For quick reference of management of smoke inhalation, see Box 2.
Oxygen therapy
Oxygen therapy is the first and most important treatment for smoke inhalation.2,6,12,30 Increased inhaled oxygen content enhances CO elimination by displacing CO from hemoglobin binding sites.3,13 The half-life of COHb when breathing room air is approximately 4 to 6 hr but decreases to 2 hr and 1 hr on 50% and 100% inspired oxygen, respectively.13,22 Thus, oxygen should be administered as soon as possible, initially at the highest available percentage, to patients with signs of smoke inhalation, then titrated down based on response to treatment.2,6
Noninvasive (conventional) oxygen supplementation via flow-by, face mask, or oxygen cage is typically used at presentation. The highest inspired oxygen concentration with flow-by oxygen is about 30% to 40%.33 Nasal prongs or bilateral oxygen cannulas can also be considered; bilateral nasal cannulas may provide up to 70% inspired oxygen.33 Placing an appropriately sized animal in an oxygen cage allows for maximal inspired oxygen concentrations of 60%.33 In cases with severe respiratory compromise, more advanced oxygen administration methods such as high-flow oxygen therapy or mechanical ventilation may be necessary.6,12,21,34 No matter the modality, provision of oxygen will lead to rapid (within hours) improvement of clinical signs attributable to CO intoxication.
In people with CO poisoning, the use of hyperbaric oxygen therapy (HBOT) can decrease the half-life of the COHb to only 20 to 30 min3,21; however, its use remains controversial in human smoke inhalation cases.12,13 HBOT has limited availability in veterinary medicine but is becoming more prevalent. To the authors’ knowledge, there are no reports on the use of HBOT therapy for clinical smoke inhalation in the veterinary literature at this time. Regardless of the method used, supplemental oxygen should be humidified in some manner to reduce dehydration of the upper airways and promote mucociliary clearance of particulate matter and secretions resulting from smoke inhalation.26
HCN intoxication therapy
In cases of suspected concurrent HCN poisoning, administration of hydroxocobalamin is the treatment of choice in humans. Hydroxocobalamin binds HCN to form cyanocobalamin (vitamin B12) and has a rapid onset of action without serious side effects.12,17,21 Any excess vitamin B12 is excreted through the kidneys. In an induced canine model of cyanide toxicity, 75 mg/kg and 150 mg/kg intravenous hydroxocobalamin resulted in 21% and 0% mortality compared to 82% in the placebo group.35
Fluid resuscitation
Adequate fluid resuscitation with balanced isotonic crystalloids is generally recommended in both the human and veterinary literature for smoke inhalation injury.2,6,12,23 Some human studies report approximately 25% to 40% higher fluid resuscitation needs in smoke inhalation patients due to increased insensible (i.e., evaporative) losses through the lungs.2,21 No such evidence exist in veterinary medicine, but it is reasonable to infer that veterinary patients may have similar losses. Patients with burns in addition to smoke inhalation have a significantly higher fluid demand.9,21,23 However, overzealous fluid administration can exacerbate pulmonary edema in smoke inhalation patients.21,23 Fluid therapy must be monitored vigilantly: overresuscitation should be avoided because it may worsen pulmonary function, cause myocardial edema, pleural or pericardial effusion, and lead to dilutional coagulopathy.2,6,21,23
Anxiolysis and pain management
Adequate anxiolysis with mild sedation is often required to enable proper animal handling and supportive care. Butorphanol can provide adequate sedation without respiratory or cardiovascular compromise and is generally considered a safe option in smoke inhalation patients without significant burn wounds.30 Acepromazine can also be considered in normotensive patients without burns.30 Burn wounds can be extremely painful, and multimodal therapy that includes full mu opioids (i.e., methadone, hydromorphone, fentanyl, etc.) and other drugs such as ketamine may be required to provide adequate analgesia in burn patients.23
Airway management
The presence of significant facial burns, progressive upper airway swelling, severe neurologic impairment, and/or presence of concurrent severe burn shock should prompt the clinician to strongly consider endotracheal intubation.2,7 In severe cases, early intubation can prevent respiratory obstruction and the need for rapid tracheostomy because progression of mucosal edema may make intubation more challenging over time.2,22
Pulmonary physiotherapy can aid in clearance of airway secretions and debris. In humans, therapeutic coughing and deep breathing exercises are encouraged.2,12 In animals, correctly performed chest physiotherapy (gentle coupage, prolonged slow expiration, and assisted cough), regular patient rotation to discourage atelectasis, and early ambulation (as permitted by other concurrent injuries) may help mobilize excess secretions and improve breathing.6,36
Empirical use of β2 agonists may help to counteract severe bronchospasm, decrease airway resistance, and enhance mucociliary clearance.2,12 The use of terbutaline, aminophylline, and/or inhaled albuterol have been described as options for treatment in veterinary sources.6
Nebulization may help moisten secretions and can be used as a method of drug delivery to the affected tissues. Use of nebulized epinephrine, heparin, and n-acetyl cysteine (NAC) have been reported in humans for treatment of smoke inhalation injury.2,9,10,19 Epinephrine causes vasoconstriction to reduce airway edema and dilates terminal bronchioles to improve alveolar ventilation. The use of nebulized epinephrine at a dose of 0.05 mg/kg added to 0.9% NaCl to make up a 5 mL solution was successful to decrease airway edema in dogs with brachycephalic obstructive airway syndrome in a recent study and might also be applicable to smoke victims.37 Heparin inhibits thrombin via antithrombin activation to help weaken fibrin cast formation in airways, and NAC has mucolytic and antioxidant properties to reduce airway obstruction and inflammation. Alternating nebulization with aerosolized heparin (10,000 IU) and 20% NAC every 2 hr showed improved pulmonary function and fewer days on mechanical ventilation in humans with smoke injury.21 However, nebulized heparin failed to show similar benefits in dogs.38 To the authors’ knowledge, no dose recommendations exist for dogs and cats for nebulized heparin or NAC.
Despite their applications for other inflammatory lung conditions, corticosteroids have failed to show benefits on survival in human smoke injury cases and may increase the risk of infection; therefore, steroids are not recommended for routine use.6,9,21
Emerging therapies including the use of antithrombin and tissue plasminogen activator to decrease fibrin production and cast formation, inducible nitric oxide synthetase inhibitors to decrease pulmonary vasodilation, extracorporeal membrane oxygenation, and use of artificial surfactant are being researched.2,39 Depending on cost and availability to veterinarians, these could provide alternative treatment options for smoke inhalation patients in the future.
Complications
Pneumonia
Bacterial bronchopneumonia is seen in 38% to 60% of human smoke inhalation victims and may increase mortality by 60%.2,12 Bacterial pneumonia in dogs following smoke inhalation has been reported and is assumed to be similar to pneumonia in humans with smoke inhalation. However, the prevalence of pneumonia after smoke inhalation in dogs is unknown.25,26,29
Prophylactic antibiotic administration is not recommended for patients exposed to smoke because it may promote the development of multidrug resistant infections.6,7,9,21 Empiric use of broad-spectrum antibiotics with both Gram negative and Gram positive spectrum can be considered in cases with signs of pneumonia, ideally after airway sampling.21,23,40 Signs of pneumonia include fever, leukocytosis with a left shift >2 days after smoke exposure, and/or radiographic evidence, including a newly developed focal, multifocal, or diffuse interstitial to alveolar pattern.7 Samples obtained via tracheal wash or bronchoalveolar lavage should be submitted for cytological analysis and culture/sensitivity testing to confirm bacterial pneumonia and selection of appropriate antimicrobial therapy.6 Empiric broad-spectrum antimicrobials should be de-escalated based on the culture and susceptibility results.12
Acute respiratory distress syndrome
In humans, acute respiratory distress syndrome (ARDS) is defined as an acute, diffuse, inflammatory form of lung injury, characterized by poor oxygenation and pulmonary infiltrates, which develops in severely ill patients within 7 days of an inciting event.41 In human burn patients, smoke inhalation is a leading cause of ARDS and is associated with significant increases in mortality.42 Therapy for ARDS is supportive, with oxygen therapy and mechanical ventilation as the main interventions. Sparse information exists in the veterinary literature on ARDS following smoke inhalation injury in dogs. Recently, two case reports described successful treatment of ARDS following smoke inhalation injury in dogs; both required mechanical ventilation.25,43
Airway obstruction
Mucosal necrosis, sloughing, and cast formation can cause tracheal and/or lower airway obstruction even 3 to 6 days after the initial event. Diffuse intraluminal tracheal obstruction with grossly necrotic tracheal tissue was recently reported in a Siberian husky 6 days after smoke inhalation.26 Bronchoscopy-guided airway cleaning is used in humans with smoke inhalation injury to remove excessive secretions and casts from the lower airways in order to improve oxygenation.2,21 It may be an option to consider in animals if airway secretions or cast formation are suspected of causing obstruction and impairing oxygenation and/or ventilation.23,26
Delayed neurological sequelae
Delayed neurological sequelae is reported in 23% to 47% of humans after CO poisoning.3,24 Although the exact pathophysiology is unknown, direct cytotoxic effects of CO are suspected. In addition to the systemic hypoxia, CO also causes cerebral vasodilation and subsequent hypotension, which is thought to play a role in exacerbating neural hypoxia.3 Neural hypoxia causes glutamate release, which leads to n-methyl D-aspartate receptor activation and ultimately cellular dysfunction and apoptosis which may lead to neurologic signs.3,13
Neurologic impairments described in dogs following smoke inhalation include altered mentation, deafness, blindness, disorientation, agitation, and seizures.25,27–29 In a case series of 21 dogs trapped in a kennel fire, 2 of the 21 dogs had progressive neurological signs, including obtunded mentation, ataxia, disorientation, deafness, blindness, and head pressing.29 One dog was euthanized, and the other made a full recovery within 6 mo.29 Both dogs had initial COHb levels higher than the average in the group (32.7% and 31% vs 24%, respectively). In another case study, a dog developed delayed neurological signs (unresponsiveness, restlessness, and constant howling) 6 days after being involved in a house fire and was subsequently euthanized on day 9 due to a lack of improvement.27 A case series of three Chihuahuas with smoke inhalation from a house fire reported development of seizures refractory to therapy 2 days after presentation, despite initial improvement in mentation.28 The concern for delayed neurological impairment should be discussed with the owners and monitoring for ataxia, disorientation, seizures or any change in the patient’s behavior is recommended. The exact timeline for these clinical signs to develop is unknown in dogs; it can be up to 6 wk in humans.3 Treatment of neurologic signs depends on the case and are mainly supportive with anticonvulsive medications, sedation, anxiolysis, and proper nursing care.
Summary
Smoke inhalation injury affects oxygen delivery to tissues, both from inhaled toxic gases as well as from direct respiratory injury from heat, chemicals, and soot. Clinical signs are primarily due to respiratory, neurological, and myocardial dysfunction. The mainstays of treatment are early oxygen administration, supportive care, tailored fluid therapy, and airway management. Common sequelae to smoke inhalation injury include bacterial pneumonia, ARDS, airway obstruction, and delayed neurologic signs. Negative prognostic indicators in smoke inhalation cases include concurrent extensive burn wounds, a lack of response or progression of respiratory signs despite oxygen therapy, and significant neurological impairment on presentation. Patients appearing normal to mildly affected on presentation generally have a favorable prognosis but should be monitored for progression of signs for a minimum of 24 hr. More severe or progressive cases often require intensive care and may benefit from poststabilization referral to 24 hr care facilities with the ability to provide high-flow oxygen therapy or mechanical ventilation.
Oxygen pathway in the body in normal situations (A) and when CO and HCN are inhaled (B). (A) In health, inhaled oxygen easily diffuses through the thin blood gas barrier from the alveolus to the blood stream and saturates the Hb binding sites.14 About 98% of the total oxygen in the blood is bound to Hb, while a small amount is dissolved in the blood, measured as pO2.15 Hb transports oxygen to the tissues where the lower tissue pO2 levels favor diffusion of oxygen from the dissolved pool into the cells followed by increased offloading of oxygen from the Hb into the dissolved pool. The net effect is to deliver oxygen to cells whose mitochondria then make use of the oxygen.15 Oxygen is converted to water, and energy is generated in the form of ATP via the electron transport chain (i.e., aerobic metabolism).44 The important enzyme in this process is cytochrome-c oxidase, which uses iron (Fe3+) and copper (Cu) to reduce oxygen to water.44 (B) CO presents a: triple threat” to tissues: (1) it displaces oxygen (O2) on the Hb binding site, decreasing the amount of carried oxygen by Hb in the blood, (2) it decreases oxygen dissociation from Hb at the tissue level, and (3) it binds to cytochrome-c oxidase in the electron transport chain, reducing mitochondrial oxygen use and causing generalized tissue hypoxia. HCN is a noncompetitive inhibitor of the mitochondrial cytochrome-c oxidase, resulting in inability of the enzyme to use oxygen, leading the cessation of cellular energy production regardless of oxygen availability. CO and HCN exposure causes systemic tissue hypoxia, resulting in severe organ dysfunction and death if exposed to large doses.17,18 ATP, adenosine triphosphate; CO, carbon monoxide; Hb, hemoglobin; HCN, hydrogen cyanide; pO2, partial pressure of oxygen.
Simplified diagram of the pathophysiology of smoke inhalation. CO, carbon monoxide, HCN, hydrogen cyanide, CNS, central nervous system, V/Q, ventilation perfusion ratio.
Contributor Notes
